This program will continue to seek a better understanding of the mechanisms by which antitumor drugs inhibit growth of malignant neoplasms to improve their use clinically. We are planning to relate in normal tissues, ascites tumors and portions of solid tumors the anabolism of fluorouracil and the drug's effect on DNA synthesis to growth inhibition and selectivity of action. We are attempting to explain the underlying biochemical mechanisms for the synergistic action of thioguanine with alkylating agents. We are examining the mechanism of the newer carcinostatic platinum drugs which do not appear to inhibit DNA synthesis selectively, and are investigating the role of cell association with respect to the mechanism of aklylating agents. The pharmacokinetics of diethylstilbestrol is being studied in man to improve the drug's activity in prostatic cancer. BIBLIOGRAPHIC REFERENCES: Edwards, G.S., Lovett, J.W., and Mandel, H.G., Nitrogen mustard and 6-thioguanine or 6-mercaptopurine: A novel combination of old drugs. The Pharmacologist 17: 201, 1975. Beck, W.T., Mandel, H.G., and Fabro, S., Physiological disposition of pentobarbital in tumor-bearing mice. Cancer Res., 35: 1333-1340, 1975.